We propose to study the mechanisms by which most patients with Graves' disease become hyperthyroid and to seek the reason why a small number remain euthyroid. We shall test four current hypotheses for each of these two major patterns of thyroid function in Graves' disease. Populations to be studied are (1) asymptomatic relatives of patients with Graves' disease, (2) patients with euthyroid Graves' disease, (3) patients with hyperthyroid Graves' disease during treatment with antithyroid drugs, and (4) such patients after discontinuance of antithyroid drugs. In each group, serial observations will be made of LATS, LATS-protector, autoantibodies and other autoimmune markers. Simultaneously, the subtlest available tests for thyroid functional abnormality will be performed, including T3 suppression tests, serum free T3/free T4 radio, and TRH stimulation tests. The autoimmune stigmata and the observations of thyroidal regulation and function will be carefully correlated at various times, viz., as susceptible patients are developing hyperthyroidism, as patients under antithyroid drug treatment are becoming normally regulable and as such patients are undergoing relapse of hyperthyroidism. Also, studies during euthyroid stages will indicate which test findings are compatible with long periods of euthyroidism. From all of these observations, it may be possible to choose among current hypotheses as to the pathogenesis of hyperthyroidism in Graves' disease. BIBLIOGRAPHIC REFERENCES: Williams, D.E., I.J. Chopra, J. Orgiazzi and D.H. Solomon. Acute effects of corticosteroids on thyroid activity in Graves' disease. J. Clin. Endocr. 41:354-361, August, 1975. Matsui, Y., G.N. Beall, I.J. Chopra and D.H. Solomon. Graves' disease and Hashimoto's thyroiditis: Differences in production of leukocyte inhibition factor (LIF). Clin. Res. 24:151A, 1976.